title: Morphological features of iPS cells generated from Fabry disease skin fibroblasts using Sendai virus vector (SeVdp).
abstract: We generated iPS cells from human dermal fibroblasts (HDFs) of Fabry disease using a Sendai virus (SeVdp) vector; this method has been established by Nakanishi et al. for pathogenic evaluation. We received SeVdp vector from Nakanishi and loaded it simultaneously with four reprogramming factors (Klf4, Oct4, Sox2, and c-Myc) to HDFs of Fabry disease; subsequently, we observed the presence of human iPS-like cells. The Sendai virus nucleocapsid protein was not detected in the fibroblasts by RT-PCR analysis. Additionally, we confirmed an undifferentiated state, alkaline phosphatase staining, and the presence of SSEA-4, TRA-1-60, and TRA-1-81. Moreover, ultrastructural features of these iPS cells included massive membranous cytoplasmic bodies typical of HDFs of Fabry disease. Thus, we successfully generated human iPS cells from HDFs of Fabry disease that retained the genetic conditions of Fabry disease; also, these abnormal iPS cells could not be easily differentiated into mature cell types such as neuronal cells, cardiomyocytes, etc. because of a massive accumulation of membranous cytoplasmic bodies in lysosomes, possibly the persistent damages of intracellular architecture.
authors.affiliation: Department of Genetic Diseases and Genomic Science, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Kawagoe
authors.forename: Takashi
authors.initials: T
authors.lastname: Higuchi
authors.forename: Manami
authors.initials: M
authors.lastname: Otaka
authors.forename: Yohta
authors.initials: Y
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Hirotaka J
authors.initials: HJ
authors.lastname: Okano
authors.forename: Mahito
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D000795:Fabry Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005822:Genetic Vectors; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology*; D000090062:Kruppel-Like Factor 4; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D029082:Sendai virus / Q000235:genetics*; D012867:Skin / Q000378:metabolism / Q000473:pathology; D014161:Transduction, Genetic
keywords: Fabry disease; Sendai virus vector; Ultrastructure; iPS cells